Mitochondrial β-amyloid in Alzheimer's disease.

It is well established that the intracellular accumulation of Aβ (amyloid β-peptide) is associated with AD (Alzheimer's disease) and that this accumulation is toxic to neurons. The precise mechanism by which this toxicity occurs is not well understood; however, identifying the causes of this toxicity is an essential step towards developing treatments for AD. One intracellular location where the accumulation of Aβ can have a major effect is within mitochondria, where mitochondrial proteins have been identified that act as binding sites for Aβ, and when binding occurs, a toxic response results.

(-)-CHANA, a fluorogenic probe for detecting amyloid binding alcohol dehydrogenase HSD10 activity in living cells.

The association of 17β-hydroxysteroid dehydrogenase 10 (HSD10) with β-amyloid in the brain is known to contribute to the progression of Alzheimer's disease. Further, it has been shown that the interaction between the purified HSD10 and β-amyloid inhibits its enzymatic activity. However, to date no system has been developed to enable the study of HSD10 activity in intact living cells.

The consequences of mitochondrial amyloid beta-peptide in Alzheimer's disease.

The Abeta (amyloid-beta peptide) has long been associated with Alzheimer's disease, originally in the form of extracellular plaques. However, in the present paper we review the growing evidence for the role of soluble intracellular Abeta in the disease progression, with particular reference to Abeta found within the mitochondria. Once inside the cell, Abeta is able to interact with a number of targets, including the mitochondrial proteins ABAD (amyloid-binding alcohol dehydrogenase) and CypD (cyclophilin D), which is a component of the mitochondrial permeability transition pore.